Markers Of Endothelial Dysfunction Research Articles

Association of hepatokines with markers of endothelial dysfunction and vascular reactivity in obese adolescents.

Obesity-induced insulin resistance (IR) is known to influence hepatic cytokines (hepatokines), including fibroblast growth factor (FGF-21), fetuin-A, and chemerin. This study aimed to investigate the association between hepatokines and markers of endothelial dysfunction and vascular reactivity in obese adolescents. A total of 45 obese adolescents were categorized into three groups based on glucose tolerance: normal glucose tolerance (NGT), prediabetes (PD), and type 2 diabetes (T2D). We examined the relationships between FGF-21, fetuin-A, and chemerin with endothelial markers (plasminogen activator inhibitor-1 [PAI-1], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion marker-1 [VCAM-1]) and vascular surrogates (brachial artery reactivity testing [BART] and peak reactive hyperemia [PRH]). Obese adolescents (age 16.2±1.2 years; 62 % female, 65 % Hispanic) with NGT (n=20), PD (n=14), and T2D (n=11) had significant differences between groups in BMI; waist-hip ratio (p=0.05), systolic BP (p=0.008), LDL-C (p=0.02), PAI-1 (p<0.001). FGF-21 pg/mL (mean±SD: NGT vs. PD vs. T2D 54±42; 266±286; 160±126 p=0.006) and fetuin-A ng/mL (266±80; 253±66; 313±50 p=0.018), were significantly different while chemerin ng/mL (26±5; 31±10; 28±2) did not significantly differ between the groups. Positive correlations were found between chemerin and both PAI-1 (r=0.6; p=0.05) and ICAM-1 (r=0.6; p=0.05), FGF-21 and PAI-1 (r=0.6; p<0.001), and fetuin-A with TNFα (r=-0.4; p=0.05). Negative correlations were found between chemerin and PRH (r= -0.5; p=0.017) and fetuin-A and PRH (r=-0.4; p=0.05). In our cohort, IR predicted higher FGF-21 levels suggesting a linear relationship may exist between the two parameters. Hepatokines can augment alterations in the microvascular milieu in obese adolescents as demonstrated by their associations with the markers PAI-1, ICAM-1, and PRH.

Serum endocan, asymmetric dimethylarginine and lipid profile in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a chronic inflammatory disease, and it is thought that subclinical inflammation persists even when there are no attacks, eventually causing endothelial dysfunction (ED) and atherosclerosis. Limited data are available about serum endocan, asymmetric dimethylarginine (ADMA) and lipid profile in children with FMF, so we aimed to evaluate these markers in children with FMF during the attack-free period. A total of 50 patients diagnosed with FMF and 50 age and sex-matched healthy children were recruited. Serum endocan, ADMA and lipid profiles were measured. Also, atherogenic indices (Castelli's risk indices I and II [CRI I and II], atherogenic index of plasma [AIP] and atherogenic coefficient [AC]) were calculated. Serum endocan, ADMA levels, low-density lipoprotein cholesterol, triglycerides, CRI II and AIP of the FMF patients were significantly higher than controls (p < 0.001). Unlike serum endocan, serum ADMA showed a positive significant correlation with total cholesterol, non-high density lipoprotein cholesterol, CRI I, AIP and AC (p < 0.001, p < 0.001, p = 0.004, p = 0.028, p = 0.004 respectively). Serum ADMA and lipid profile might be used as potential markers for endothelial dysfunction and increased cardiovascular risk in FMF patients. Theoretically, serum ADMA may affect lipid profiles and serum endocan represents an intriguing biomarker related to inflammation. Coexistence of dyslipidemia represents an additional risk factor that contributes to the onset of early atherosclerosis. A few studies investigated the role of changes in lipid profile and lipid ratios in accelerated atherosclerosis pathogenesis in FMF patients. The relationship between colchicine and lipid profile is contradictory. Although colchicine can cause dyslipidemia, it also has anti-atherosclerosis effects. Elevated ADMA level and atherogenic indices in FMF children reflect their potential role in the early detection of cardiovascular affection in FMF patients.

THE SEVERITY OF VASCULAR INFLAMMATION AND ITS RELATIONSHIP WITH CLINICAL AND FUNCTIONAL FEATURES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITHOUT CONCOMITANT CARDIOVASCULAR PATHOLOGY

The Russian Federation is one of the countries with a high prevalence of chronic obstructive pulmonary disease (COPD). In the last decade, the list of families of chemical regulators of vascular inflammation in COPD has been supplemented with information about growth factors, whose participation in the processes of regulation of vascular function seems significant. The study of the role of angiogenesis factors in patients with isolated COPD disease is insufficient at this stage and needs to be clarified. Objective. To study was to identify diagnostic and prognostic criteria for the severity of vascular inflammation and to assess its relationship with clinical and functional features in patients with COPD without concomitant cardiovascular pathology in comparison with the clinical phenotype of the disease. Material and methods. 96 patients with COPD were examined, the median age was 61 years. In addition to standard clinical, functional and laboratory research methods, the severity of vascular inflammation was assessed in all examined patients with the determination of quantitative indicators of human platelet growth AA factor and tumor necrosis factor-α (TNFα) by quantitative solid-phase enzyme immunoassay Results. In all patients with isolated COPD, regardless of the risk of developing the underlying disease, an increase in the level of platelet growth AA factor and TNFα was noted. The level of platelet growth AA factor and TNFα in patients with COPD, regardless of the risk of exacerbation, was correlated with the functional state of the lungs, clinical phenotype and severity of clinical manifestations of the disease. The value of platelet growth AA factor above 317 ng/ml in patients with COPD may be an early marker of endothelial dysfunction and a predictor of the development of hemostatic disorders and concomitant cardiovascular pathology.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

THE SEVERITY OF VASCULAR INFLAMMATION AND ITS RELATIONSHIP WITH CLINICAL AND FUNCTIONAL FEATURES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITHOUT CONCOMITANT CARDIOVASCULAR PATHOLOGY

The Russian Federation is one of the countries with a high prevalence of chronic obstructive pulmonary disease (COPD). In the last decade, the list of families of chemical regulators of vascular inflammation in COPD has been supplemented with information about growth factors, whose participation in the processes of regulation of vascular function seems significant. The study of the role of angiogenesis factors in patients with isolated COPD disease is insufficient at this stage and needs to be clarified. Objective. To study was to identify diagnostic and prognostic criteria for the severity of vascular inflammation and to assess its relationship with clinical and functional features in patients with COPD without concomitant cardiovascular pathology in comparison with the clinical phenotype of the disease. Material and methods. 96 patients with COPD were examined, the median age was 61 years. In addition to standard clinical, functional and laboratory research methods, the severity of vascular inflammation was assessed in all examined patients with the determination of quantitative indicators of human platelet growth AA factor and tumor necrosis factor-α (TNFα) by quantitative solid-phase enzyme immunoassay Results. In all patients with isolated COPD, regardless of the risk of developing the underlying disease, an increase in the level of platelet growth AA factor and TNFα was noted. The level of platelet growth AA factor and TNFα in patients with COPD, regardless of the risk of exacerbation, was correlated with the functional state of the lungs, clinical phenotype and severity of clinical manifestations of the disease. The value of platelet growth AA factor above 317 ng/ml in patients with COPD may be an early marker of endothelial dysfunction and a predictor of the development of hemostatic disorders and concomitant cardiovascular pathology.

Strong Association of Metabolic Parameters with ADMA and VCAM-1 in Normo-Weight Subjects with Metabolic Syndrome.

Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity. This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese. The study was designed using a case-control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups. Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups. Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.

Roles of endothelial cell specific molecule‑1 in tumor angiogenesis (Review).

Angiogenesis plays a crucial role in tumor growth and metastasis, and is heavily influenced by the tumor microenvironment (TME). Endothelial cell dysfunction is a key factor in tumor angiogenesis and is characterized by the aberrant expression of pro-angiogenic factors. Endothelial cell specific molecule-1 (ESM1), also known as endocan, is a marker of endothelial cell dysfunction. Although ESM1 is primarily expressed in normal endothelial cells, dysregulated ESM1 expression has been observed in human tumors and animal tumor models, and implicated in tumor growth, metastasis and angiogenesis. The precise role of ESM1 in tumor angiogenesis and its potential regulatory mechanisms are not yet conclusively defined. However, the aim of the present review was to explore the involvement of ESM1 in the process of tumor angiogenesis in the TME and the characteristics of neovascularization. In addition, the present review discusses the interaction between ESM1 and angiogenic factors, as well as the mechanisms through which ESM1 contributes to tumor angiogenesis. Furthermore, the reciprocal regulation between ESM1 and the TME is explored. Finally, the potential of targeting ESM1 as a therapeutic strategy for tumor angiogenesis is presented.

Interleukin-6 (IL-6) as a Marker of Endothelial Dysfunction Confirmed Using Flow Mediated Dilatation in Active Smoker

Background: The pro-inflammatory cytokine interleukin-6 (IL-6) is thought to be the catalyst for endothelial dysfunction caused by smoking. Flow-mediated dilatation (FMD) is a non-invasive method to identify the development of blood vessel endothelial dysfunction at an early stage. However, several studies have not sufficiently explained how smoking and IL-6 interact. Objective: This study focuses on the role of Interleukin-6 (IL-6) in the process of endothelial dysfunction confirmed using non-invasive modalities such as Flow Mediated Dilatation (FMD) in smokers related to the risk of cardiovascular disease in the future with the hope of providing insight in education to smokers to quit smoking. Material and Methods: In this study, we gathered 116 male participants, of which 56 were nonsmokers, and 60 were smokers, and we used IL-6 and FMD testing. SPSS for Windows version 23 will be used to analyze the data. Result: According to the analysis of laboratory tests, the average IL-6 level in light smokers was 67.7±3.2 and in moderate smokers it was 95.111.0; with a p-value of 0.009, indicating a significant difference among the groups. The average FMD in the smoking group was 5.4±0.4% (p-value 0.000), whereas the average FMD in the non-smoker samples was 10.9±0.9%. We also looked at the average FMD among light and moderate smokers based on Brinkman Index, which was 5.5±0.4% and 5.00.4%, with a p-value of 0.780, indicating no significant difference between the groups Conclusion: Compared to non-smokers, this study demonstrates a correlation between IL-6 and smoking activity. However, there was no statistically significant difference between the prevalence of endothelial dysfunction and the degree of smoking dependence in this investigation.

Erectile function in men with COVID-19 six months after recovery

Background. Based on the results of epidemiological studies, it was found that coronavirus disease 2019 (COVID-19) affects men more often than women. Among COVID-19 complications, erectile dysfunction is considered a marker of endothelial dysfunction and one of the main factors for the development of cardiovascular diseases. Lower total and free testosterone levels are predictors of adverse prognosis in males with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Testosterone deficiency syndrome is considered an independent risk factor of cardiometabolic disorders. The purpose of the study is to investigate the state of erectile function in men who suffered from COVID-19 six months after recovery. Materials and methods. Seventy-two men suffering from COVID-19 and being treated in an infectious disease hospital were examined 6.90 ± 0.29 months after recovery. Their average age was 45.23 ± 3.01 years. The control group included 18 conditionally healthy men aged 43.18 ± 2.90 years. The state of erectile function was assessed using the International Index of Erectile Function (IIEF). The concentration of testosterone was determined by the enzyme-linked immunosorbent assay with DRG (Germany) and DiaMetra (Italy) kits. All measurements were performed on the Stat Fax 3200 analyzer. Statistical comparison of the obtained results between groups was performed according to the Student’s test. A value of p &lt; 0.05 was considered to be signifi­cant. Results. In addition to erectile dysfunction, as evidenced by a reduced corresponding integrative indicator “erectile function” of IIEF-15 in men with COVID-19, a decrease in sexual desire was found, as well as a deterioration of sensations in the form of a decrease in ejaculation frequency and orgasmic sensations during sex contacts. The average serum level of total testosterone was 10.9 nmol/l and was significantly reduced compared to that in the control group. Analysis of individual indicators showed that testosterone level was decreased in 10 patients and was within the normal range in 13 men with COVID-19. The average serum concentration of total testosterone in the examined men after the disease was 10.73 ± 1.07 nmol/l and was significantly reduced compared to that of the control group. Conclusions. There was an erectile dysfunction in men who suffered COVID-19, it was confirmed by a probable decrease in IIEF-15 score and integrative indicators of erectile function. A significant decrease in the blood concentration of total testosterone was detected in the examined men, which may be one of the causes of erectile dysfunction. Large-scale prospective, randomized, controlled trials in patients infected with SARS-CoV-2 are needed to provide an understanding of the molecular mechanisms that cause erectile dysfunction.

Endothelin-1 indices in patients with leptospirosis of various severity degrees and their changes under the influence of seven-day treatment

Introduction. Leptospirosis is one of the most common zoonoses in the world, pathogenesis of which is based on the damage of vascular endothelium. Violation of endothelial functions leads to damage of these cells plasma membranes, loss of vascular integrity, ischemia, necrosis, and, finally, the development of organ dysfunction. In current literature there is sparce information concerning endothelial dysfunction in patients with leptospirosis, therefore the development and standardization of methods for the assessment of vascular endothelium imbalance in patients with leptospirosis of different severity degrees is an urgent task. Detection of endothelin-1 (ET-1) one of the best markers of endothelial dysfunction, can become an important tool for predicting the severity of the disease. The aim of the study. To investigate ET-1 indices in patients with leptospirosis of different severity degrees and to estimate their changes after the seven-day treatment. Materials and methods. ET-1 content in the blood serum of patients with diagnosed leptospirosis was detected by ELISA method. Absolute values were compared using Mann-Whitney test (U-test); the results were statistically processed using Fisher’s bilateral test (F-test). Correlation analysis was carried out according to Spearman’s method. The difference was considered statistically significant with p less than 0.05. Results. ET-1 content was detected at time of hospitalization and after 7 days of leptospirosis treatment. Patients (n = 43) were divided into two groups depending on the severity of leptospirosis course: the first group with a moderate course included 21 patients; second group with a severe course included 22 patients; the control group consisted of 20 healthy individuals. Both groups of leptospirosis affected patients demonstrated significantly higher ET-1 concentration in comparison with the control group (p less than 0.01). Moreover, the proportion of patients with high (more than 5.5 pg/ml) concentration of ET-1 in the blood post the 7 days treatment was documented in 13.3% patients of the first group, and 43.8 % patients of the second group (p less than 0.05). It was also estimated that in both groups patients 7 days treatment of leptospirosis induced a credible increase in the concentration of ET-1 (p less than 0.05). Conclusions. Our results claim that at time of hospitalization and after 7 days treatment both groups of leptospirosis affected patients demonstrated significantly higher level of ET-1 in comparison to control group individuals (p less than 0.01). 7 days of leptospirosis treatment caused a credible enhancement of ET-1 content (p less than 0.05). Patients with a severe course of leptospirosis after 7 days treatment exposed significantly higher ET-1 concentration compared to patients with moderate course (p less than 0.05).

Impact of CytoSorb Hemoadsorption Therapy on Fluid Balance in Patients with Septic Shock.

Recent in vitro studies have investigated the effects of hemoadsorption therapy on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but, to this day, there are no clinical studies proving whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We retrospectively analyzed data on administered fluid volumes and catecholamines in 124 septic shock patients. We collected catecholamine and volume requirements and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. Regarding the entire study cohort, our findings revealed a significant reduction in fluid balance at 72 h (T72) compared to both baseline (T0) and the 24 h mark (T24). Fluid balances from T72-T0 were significantly lower in hospital survivors compared with non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings suggest that the applied treatment regimen including hemoadsorption therapy is associated with a reduced positive fluid balance paralleled by reductions in vasopressor needs, suggesting a potential positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights on the multiple effects of hemoadsorption treatment in septic shock patients.

Method of comprehensive physiotherapy of dental patients after COVID-19

To describe the mechanism of action and clinical effectiveness of the developed combined physiotherapy method, including the induced technique of piracetam iontophoresis on the frontooccipital technic and acupuncture laser therapy in dental patients with complaints of edentulism progression after COVID-19 on the basis of the analysis of single studies on the post-COVID loss of teeth treatment. A number of patients equal 120 who complained of tooth loss after COVID-19 during the past 6 months were examined. The following initial and end points were considered: dental bleeding and inflammation scores, vascular and endothelial dysfunction markers - levels of intercellular adhesion molecules and their receptors (SlCAM-1, SVCAM-1, VEGF-A, ET-1) before and after treatment. Negative correlation between VEGF-A (pg/ml) concentration in peripheral blood serum and sVCAM-1 (ng/ml) level in the examined patients (r=0.4830, p<0.05) and strong inverse correlation between slCAM-1 (ng/ml) level and sVCAM-1 (r=0.7696, p<0.01) have been established. More significant effects after application of the combined induced method on the head's structures and laser acupuncture have been noted than after acupuncture laser exposure and after inducing technique separately, namely in the form of dental inflammation score correction by 1.76 times (p<0.001), decrease of bleeding score by 2.6 (p<0.05), decrease of concentration of SVCAM-1 by 1.7 times and SlCAM-1 by 2 times (p<0.001), increase of endothelin level by 1.7 times as well as the initial low VEGF-A (pg/ml) by 1.5 times (p<0.01). The developed physiotherapeutic complex, which includes laser acupuncture physiotherapy and induced technique of 5% piracetam iontophoresis, can potentially be considered as a physioprophylactic and therapeutic model of post-COVID edentulism.

The Impact of Endothelial Dysfunction on the Course of Metabolically Associated Liver Disease in Combination with Subclinical Hypothyroidism

Background. Intrahepatic endothelial dysfunction is involved in many diseases, including fatty liver disease, and in combination with other numerous mechanisms may play a role in atherosclerosis in hypothyroidism. It is possible that endothelial dysfunction markers may be important in assessing the risk of cardiovascular events in patients with metabolic-associated fatty liver disease (MAFLD) in combination with subclinical hypothyroidism. Aims. The aim of this study was to evaluate changes in endothelial dysfunction markers in patients with MAFLD in combination with subclinical hypothyroidism. Methods. We studied 298 patients aged 40-69 years with a history of MAFLD. Of these, 128 patients had a verified diagnosis of both MAFLD and subclinical hypothyroidism. In such cases, the morphological state of the vascular endothelium was assessed by counting circulating desquamated epithelial cells (CDEC) and vascular endothelial growth factor (VEGF-A) in the blood using phase-contrast microscopy and the value of these parameters was in comparison todepending on the level of thyroid stimulating hormone, insulin, age, and cardiovascular risk. Results. It was found that the level of CDEC and VEGF-A was increased in patients with MAFLD and subclinical hypothyroidism. On the one hand, thyroid stimulating hormone levels were found to be associated with endothelial dysfunction and hyperinsulinemia. On the other hand, endothelial dysfunction indices also have links with the degree of cardiovascular risk. Patients with moderate and high cardiovascular risk have a relationship between CDEC and levels of triglycerides, C-reactive protein, and сardiovascular diseases. The levels of VEGF-A and CDEC were significantly higher in the adult age group. VEGF-A levels &gt; 273 pg/mL were associated with abnormalities in the studied parameters, including those reflecting of the liver. Conclusion. Patients with MAFLD in combination with hypertension have elevated levels of CDEC and VEGF-A, which affects the involvement of these factors in the mechanisms of endothelial dysfunction in this category. Markers of endothelial dysfunction can be used to assess the prediction of possible cardiometabolic risk.

Некоторые маркеры эндотелиальной дисфункции у пациентов с артериальной гипертензией с сочетанной патологией

Некоторые маркеры эндотелиальной дисфункции у пациентов с артериальной гипертензией с сочетанной патологией

Показатели оксидативного стресса и дисфункции эндотелия при сахарном диабете 2-го типа: риски и фокус на диетотерапию

Type 2 diabetes (T2D) is a chronic metabolic disease that poses a significant threat to public health worldwide. Carbohydrate metabolism disorders in T2D are closely related to oxidative stress. Numerous vascular complications are the main cause of disability and mortality in this disease. Objective. Comparative evaluation of the indices of oxidative stress and endothelial dysfunction with anthropometric and biochemical parameters in T2D patients. Patients and methods. The study included 55 patients with T2D and 58 patients with class 1–3 obesity without diabetes. Patients with T2D received a standard treatment with oral sugar-lowering drugs, hypolipidemic and hypotensive therapy as indicated. All patients underwent measurements of anthropometric parameters (height, weight, body mass index), indices of carbohydrate and lipid metabolism, antioxidant status and endothelial dysfunction, triglycerides-glucose index, and pulse wave velocity. Statistical processing of the results was performed using SPSS 23.0 software. Results. Several correlations were found between oxidative stress indices and clinical and metabolic parameters characterizing the state of carbohydrate and lipid metabolism and anthropometric indices in patients with T2D. The level of high-sensitivity C-reactive protein was almost twice as high in T2D patients compared to patients with obesity (11.1 ± 2.58 mg/L and 6.77 ± 1.11 mg/L, respectively). A negative correlation between the levels of superoxide dismutase and fasting blood glucose was determined (r = -0.30, p &lt; 0.005). Conclusion. The study revealed a strong correlation between oxidative stress indices, markers of endothelial dysfunction and cardiometabolic disorders in patients with T2D. The influence on oxidative stress/antioxidant defense indices may become an additional therapeutic link in the treatment of T2D patients. Key words: reactive oxygen species, endothelial dysfunction, oxidative stress, type 2 diabetes

Differential blood-based biomarkers of subcortical and deep brain small vessel disease.

Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group. We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ1-40, Aβ1-42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ1-40 and Aβ1-42 were significantly lower in patients with deep LS (p < 0.0001). Aβ1-42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.

Inducible Nitric Oxide Synthase Gene Polymorphism and Markers of Pro-inflammatory Endothelial Dysfunction in Coronary Artery Disease: Case Control Study in North Indian Population

Inducible Nitric Oxide Synthase Gene Polymorphism and Markers of Pro-inflammatory Endothelial Dysfunction in Coronary Artery Disease: Case Control Study in North Indian Population

Эндотелиальная дисфункция у пациентов с коронавирусной инфекцией COVID-19

Endothelial dysfunction is the main cause of thrombotic complications and unfavorable disease outcome in COVID-19. The study of markers of endothelial dysfunction in patients with COVID-19 will help to determine additional directions for the treatment of hemostatic disorders. The purpose — to evaluate the diagnostic significance of endothelial dysfunction markers in moderate and severe forms of COVID-19. Material and methods. The study was carried out in 28 patients with COVID-19 hospitalized at the Republic Clinical Infectious Diseases Hospital (Kazan) from 02.16.2023 to 03.07.2023. The median age of patients was 66.5 years. The control group consisted of 20 healthy people of the same age. Results. It was found that moderate and severe forms of COVID-19 are accompanied by increased values of D-dimer and VWF in the blood, the medians of which were 2.6 and 1.9 times higher than control values, respectively. No significant differences in the values of P-selectin and thrombomodulin were detected in the compared groups. A moderate correlation was established between the level of P-selectin and the absolute number of neutrophils in the blood. It was found that the values of D-dimer and thrombomodulin were significantly higher in patients with COVID-19 who had two or more comorbid diseases. The high likelihood ratios of FFB and D-dimer positivity (LR+ = 8.4) allow considering them as reliable parameters for assessing endothelial dysfunction in patients with COVID-19. Conclusion. Endothelial dysfunction in COVID-19 disease is manifested by increased levels of D-dimer and VWF in the blood. The identified changes indicate the possibility of using medications that neutralize VWF in addition to anticoagulant drugs.

Disturbed flow impairs MerTK-mediated efferocytosis in aortic endothelial cells during atherosclerosis.

Background: MER proto-oncogene tyrosine kinase (MerTK) is a key receptor for efferocytosis, a process for the clearance of apoptotic cells. MerTK is mainly expressed in macrophages and immature dendritic cells. There are very limited reports focused on MerTK biology in aortic endothelial cells (ECs). It remains unclear for the role of blood flow patterns in regulating MerTK-mediated efferocytosis in aortic ECs. This study was designed to investigate whether endothelial MerTK and EC efferocytosis respond to blood flow patterns during atherosclerosis. Methods: Big data analytics, RNA-seq and proteomics combined with our in vitro and in vivo studies were applied to reveal the potential molecular mechanisms. Partial carotid artery ligation combined with AAV-PCSK9 and high fat diet were used to set up acute atherosclerosis in 4 weeks. Results: Our data showed that MerTK is sensitive to blood flow patterns and is inhibited by disturbed flow and oscillatory shear stress in primary human aortic ECs (HAECs). The RNA-seq data in HAECs incubated with apoptotic cells showed that d-flow promotes pro-inflammatory pathway and senescence pathway. Our in vivo data of proteomics and immunostaining showed that, compared with WT group, MerTK-/- aggravates atherosclerosis in d-flow areas through upregulation of endothelial dysfunction markers (e.g. IL-1β, NF-κB, TLR4, MAPK signaling, vWF, VCAM-1 and p22phox) and mitochondrial dysfunction. Interestingly, MerTK-/-induces obvious abnormal endothelial thickening accompanied with decreased endothelial efferocytosis, promoting the development of atherosclerosis. Conclusions: Our data suggests that blood flow patterns play an important role in regulating MerTK-mediated efferocytosis in aortic ECs, revealing a new promising therapeutic strategy with EC efferocytosis restoration to against atherosclerosis.

Comparison of vascular cell adhesion molecule 1 (VCAM-1) during pregnancy, after placental detachment and during puerperium between normal and pregnancy with COVID-19.

Pregnant women have a number of physiological changes that lower the immune responses to avoid embryonic rejection, which increases the risk of problems after contracting coronavirus disease 2019 (COVID-19). Multiple inflammatory cytokines are dysregulated in this process and expressed inappropriately during systemic inflammatory responses associated with COVID-19. The aim of the study was to compare the levels of vascular cell adhesion molecule 1 (VCAM-1), a marker of endothelial damage in pregnancies with and without COVID-19. A cohort prospective study was conducted at H. Adam Malik General Hospital and the Universitas Sumatera Utara Hospital, Indonesia. Pregnant women without COVID-19 and pregnant women with moderate and severe degrees of COVID-19 were recruited. The level of VCAM-1 was measured at three different time points (during pregnancy, within an hour of placental detachment, and 24 hours postpartum). The ANOVA and Student t-test were used to compare the VCAM-1 levels among different time points and between groups, respectively. The mean VCAM-1 levels at the hospital admission, one hour of placental detachment and 24 hours postpartum in non-COVID-19 and COVID-19 pregnancies were 591.29 vs 1176.27 pg/mL; 558.2 vs 1136.2 pg/mL; and 508.59 vs 985.2 pg/mL, respectively. There was a significant different in VCAM-1 levels in normal pregnancy at the time of hospital admission, one hour after detachment of the placenta and 24 hours postpartum (p=0.04). The mean VCAM-1 levels in pregnant women with COVID-19 also had significant differences between three time points (p=0.033). The levels of VCAM-1 were statically higher among pregnancy in the COVID-19 group compared to the non-COVID-19 group during hospital admission (p=0.023), one hour after placenta detachment (p=0.040) and 24 hours postpartum (p=0.043). The results suggested the usefulness of identifying the VCAM-1 level as a marker of endothelial dysfunction in pregnancy with COVID-19.